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Open Access Antitumor Activity of Mannan–Methotrexate Conjugate In Vitro and In Vivo

Conjugation of anticancer drugs with different carriers has been extensively studied recently as a potential method of obtaining improved drug forms. The conjugation often results in the increase of the therapeutic effect, alteration of a toxicity profile, and/or selective targeting of therapeutic agent to the tissue of interest. We have synthesized mannan–methotrexate conjugate by means of methotrexate anhydride and studied its antitumor properties both in vitro and in vivo in comparison with free methotrexate. Mannan–methotrexate conjugate showed significantly improved antitumor activity compared to free methotrexate in the model of P388 mouse leukemia disseminated in the peritoneal cavity treated with intraperitoneally injected chemotherapy. Conversely, the antitumor effects of free methotrexate and mannan-methotrexate conjugate were comparable when leukemia was implanted subcutaneously and chemotherapy agents were administered intravenously. These results suggest that mannan–methotrexate conjugate should be further investigated as a potential therapeutic agent for intraperitoneally disseminated tumors.

Keywords: Antitumor; Cancer; Conjugates; Leukemia; Mannan; Methotrexate

Document Type: Research Article

Affiliations: 1: Laboratory of Biomedical Chemistry, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland 2: Laboratory of Experimental Anticancer Therapy, Department of Experimental Oncology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland, Kopvillem Institute of Medical Physics, 690068 Vladivostok, Russia 3: Laboratory of Experimental Anticancer Therapy, Department of Experimental Oncology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland, Jan Dlugosz Academy, 42-201 Czestochowa, Poland 4: Laboratory of Experimental Anticancer Therapy, Department of Experimental Oncology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland 5: Laboratory of Biomedical Chemistry, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland, Jan Dlugosz Academy, 42-201 Czestochowa, Poland

Publication date: 01 September 2007

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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.

    From Volume 23, Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics is Open Access under the terms of the Creative Commons CC BY-NC-ND license.

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